Clinical Development and Regulatory Challenges - The company is currently in clinical development with one product candidate, plogosertib, a PLK 1 inhibitor for esophageal cancer and acute leukemia [132]. - Clinical trials for plogosertib may require several more years to complete and could extend beyond available funding [132]. - The company has faced challenges in clinical trials, including a failed SEAMLESS Phase 3 study that did not meet its primary endpoint [133]. - Delays in securing clinical investigators or trial sites could impact the timeline for clinical trials and regulatory approvals [135]. - The company may experience increased development costs due to enrollment delays in clinical trials, potentially harming commercial prospects for plogosertib [138]. - The FDA and other regulatory authorities have substantial discretion in the approval process, which can be lengthy and unpredictable [146]. - The company has not yet submitted a marketing application for plogosertib and has limited experience in conducting the necessary clinical trials [146]. - The use of biomarkers in drug development is not scientifically validated, which may lead to inefficient resource allocation [142]. - The company has not obtained regulatory approval for any drug candidate, and future candidates may also face significant hurdles [146]. - The company may face delays in receiving regulatory approval for plogosertib due to various factors, including disagreements with regulatory authorities on trial design [148]. - Delays in clinical trials may harm the approval and commercial prospects of the product candidate, potentially increasing costs and delaying revenue generation [149]. - Regulatory authorities may approve drug candidates for fewer indications than requested, impacting commercial potential [150]. - Undesirable side effects from the product candidate could lead to delays in marketing approval and limit commercial potential [151]. - The FDA and other regulatory authorities may require costly post-marketing studies or impose restrictions on the product's marketing [157]. - Regulatory approvals may be subject to limitations and ongoing compliance requirements, which could affect market acceptance [163]. - The time required for regulatory approval is unpredictable and can take many years, influenced by various factors [160]. Competition and Market Dynamics - Competition is intense, with numerous drug candidates in development that may be more effective or less expensive [171]. - The company is highly dependent on market acceptance among healthcare providers and payors, which is influenced by factors such as safety, efficacy, and pricing [178]. - Reimbursement decisions by third-party payors may adversely affect pricing and market acceptance of the company's products, potentially limiting commercialization [180]. - Future product candidates may face competition from generic and follow-on drug products sooner than anticipated, impacting potential revenue [172]. - The FDA's approval process for generic drugs allows competitors to enter the market, which could negatively affect the company's future revenue and profitability [174]. Financial Condition and Capital Requirements - The company has incurred operating losses since its inception in 1996, with an accumulated deficit of $439.5 million as of December 31, 2024 [229]. - The net loss for the year ended December 31, 2024, was $11.2 million, compared to a net loss of $22.5 million for the year ended December 31, 2023 [229]. - As of December 31, 2024, the company's cash and cash equivalents were $3.1 million, raising substantial doubt about its ability to continue as a going concern for the next year [232]. - The company expects to incur significant losses for several years as it continues research and development of drug candidates and seeks regulatory approvals [229]. - The company may face challenges in raising additional capital, which could lead to further dilution of existing stockholders' interests [233]. - The company faces substantial additional funding requirements to support research, clinical trials, and commercialization efforts, which may be impacted by current economic conditions [250][251]. Legislative and Regulatory Environment - Legislative and regulatory changes in healthcare could continue to impact the business and financial condition of the company [182]. - The Affordable Care Act (ACA) has significantly impacted the U.S. pharmaceutical industry, increasing Medicaid rebates and establishing a 70% point-of-sale discount for Medicare Part D beneficiaries during coverage gaps [196]. - The American Rescue Plan Act of 2021 eliminates the statutory cap on Medicaid drug rebates, effective January 1, 2024, which could affect pricing strategies [198]. - Starting in 2023, manufacturers must pay a rebate to the federal government if drug prices increase faster than inflation, with negotiations for select Medicare Part D drugs beginning in 2026 [203]. - The Inflation Reduction Act of 2022 allows the Secretary of HHS to implement provisions through guidance, creating uncertainty about its effects on drug pricing [203]. - Increased scrutiny over pharmaceutical pricing has led to Congressional inquiries and proposed legislation aimed at enhancing transparency and reforming reimbursement methodologies [200]. - The U.S. Supreme Court's decision in December 2020 allows states to regulate pharmaceutical benefit managers, potentially leading to more aggressive state-level regulations [206]. - Legislative changes at both federal and state levels may limit government payments for healthcare products, impacting demand and pricing pressures on the company's products [209]. - The company anticipates that future healthcare reforms could have a material adverse effect on the U.S. healthcare industry, particularly regarding access and financing [199]. Operational Risks and Compliance - The company is experiencing a tight labor market with an unemployed-to-job-openings ratio of 0.9, leading to increased costs and challenges in recruitment [186]. - The commercialization of products will depend on the ability to develop effective sales and marketing capabilities, which are currently lacking [192]. - The company may face delays in product supply if third-party manufacturers do not meet quality or timeliness standards [189]. - Regulatory compliance costs are increasing due to evolving privacy laws, which may adversely affect the company's financial condition [225]. - The company has not yet self-certified under the newly adopted EU-U.S. Data Privacy Framework, which may complicate data transfer processes [217]. - The company is vulnerable to economic instability, which could adversely impact its business strategy and financial performance [234]. - The company may be subject to significant penalties for noncompliance with privacy regulations, including fines of up to €20 million or 4% of annual global revenues [218]. - Cybersecurity incidents pose a risk to the company's sensitive data and operations, with potential legal and reputational consequences [256][258]. - Disruptions at the FDA and other agencies could adversely affect the company's ability to review and approve new products, impacting business operations [238][239]. Intellectual Property and Legal Risks - Intellectual property rights are crucial for commercial success; inadequate enforcement could harm the company's competitive position [275]. - The company may be subject to claims regarding the wrongful use of trade secrets from former employers of its employees, which could lead to litigation and loss of valuable rights [281]. - The company relies on trade secret protection for its proprietary technology and processes, but enforcing these protections can be difficult and costly [282]. - There are risks of infringing on third-party intellectual property rights, which could delay or prevent the commercialization of drug candidates [283]. - The company is aware of several published patent applications that could potentially restrict its research and development operations [284]. - The company may incur substantial costs due to litigation related to patent and intellectual property rights, which could divert management's attention from business operations [285]. Stock and Market Considerations - The company executed a 15:1 reverse stock split on December 18, 2023, to regain compliance with Nasdaq's minimum bid price requirements [246]. - Nasdaq notified the company on February 25, 2025, that it has regained compliance with the equity requirement in Listing Rule 5550(b)(1) [247]. - The company does not anticipate paying cash dividends on its common stock in the foreseeable future, relying instead on capital appreciation for returns [325]. - The number of shares of common stock registered for resale is significant and could exert downward pressure on the market price of the common stock [326]. - The company is exposed to risks related to marketable securities, which may be impacted by market volatility and credit restrictions [328]. - The company may face substantial costs and management distraction from potential litigation related to its securities [320]. - The automatic conversion of convertible preferred stock could lead to significant fluctuations in the price of common stock [324]. - The company’s ability to pay cash dividends on preferred stock is limited by Delaware law and its current financial condition [314].

Revenue Performance - Revenue for the three and nine months ended September 30, 2024, was $10,000 and $43,000, respectively, compared to $16,000 and $389,000 for the same periods in 2023, indicating a decline of 37.5% and 89.0% year-over-year [118]. - Revenue for the three months ended September 30, 2024, was $10,000, a decrease of 38% from $16,000 in the same period of 2023 [150]. Financial Position - As of September 30, 2024, the company had cash and cash equivalents of $2.98 million, down from $5.94 million in 2023, indicating a liquidity challenge [137]. - The accumulated deficit as of September 30, 2024, was $436.4 million, reflecting significant losses since inception [137]. - The company has received a notice from Nasdaq regarding non-compliance with the Equity Rule due to stockholders' equity being less than $2.5 million, with a stockholders' equity deficit of approximately $0.97 million as of September 30, 2024 [134][136]. Operating Activities - The company reported a net cash used in operating activities of $6.6 million for the nine months ended September 30, 2024, a decrease of $5.6 million from $12.2 million in the same period of 2023 [139]. - General and administrative expenses for the nine months ended September 30, 2024, were $4.4 million, down from $4.8 million in 2023, reflecting an 8% decrease [157]. Research and Development - Total research and development expenses decreased by $9.9 million from $15.6 million for the nine months ended September 30, 2023, to $5.8 million for the same period in 2024, representing a 63% reduction [154]. - Research and development expenses for the transcriptional regulation program decreased by $6.6 million, primarily due to decreases in manufacturing and non-clinical expenditure [154]. - The Phase 1/2 study of plogosertib has treated 15 patients with no dose-limiting toxicities observed, indicating potential for further development in various cancer types [131][132]. - Fadraciclib, a CDK2/9 inhibitor, is being evaluated in a Phase 1/2 study with 47 heavily pretreated patients dosed, showing good tolerability and preliminary efficacy in certain cancer types [120][121]. - In the ongoing Phase 2 study of fadraciclib, two partial responses were reported in patients with T-cell lymphoma, and a 22% reduction in tumor burden was observed in a patient with squamous non-small cell lung cancer [123]. Future Outlook - The company is currently investigating ways to raise additional capital through private equity financing or strategic transactions due to substantial doubt about its ability to continue as a going concern [133]. - The company has substantial doubt about its ability to continue as a going concern for at least twelve months from the issuance date of the Quarterly Report due to reliance on additional financing [149]. - Future funding requirements will depend on the ability to generate product revenue and the availability of funds in equity markets [144]. - Overall research and development expenses for the year ended December 31, 2024, are anticipated to decrease compared to 2023, focusing primarily on clinical trial costs [155]. - The company expects to fulfill its obligations under the clinical manufacturing agreement by the fourth quarter of 2024 [151]. Other Income - Other income decreased by $195,000 from $235,000 for the nine months ended September 30, 2023, to $40,000 for the same period in 2024 [159]. - Total income tax benefit for the nine months ended September 30, 2024, was $2.0 million, a decrease of 23% from $2.6 million in the same period of 2023 [164].

Financial Performance - The net loss for the three months ended September 30, 2024, was $2.0 million, compared to $6.0 million for the same period in 2023, reflecting improved financial performance[10] - Net cash used in operating activities was $6.6 million for the nine months ended September 30, 2024, compared to $12.2 million for the same period in 2023, indicating a reduction in cash burn[5] Cash and Liquidity - As of September 30, 2024, cash equivalents totaled $3.0 million, down from $3.4 million as of December 31, 2023[5] - The company is investigating ways to raise additional capital through private equity financing or strategic transactions to avoid potential delisting from Nasdaq[6] - The company has received an extension until December 24, 2024, to regain compliance with Nasdaq's minimum stockholders' equity requirement[4] Expenses - Research and development (R&D) expenses were $1.0 million for the three months ended September 30, 2024, a significant decrease from $5.2 million for the same period in 2023[7] - General and administrative expenses for the three months ended September 30, 2024, were $1.2 million, down from $1.6 million for the same period in 2023, primarily due to reduced stock compensation costs[8] Revenue - The company reported collaboration and research and development revenue of $10,000 for the three months ended September 30, 2024, compared to $16,000 for the same period in 2023[15] Tax Credits - United Kingdom research & development tax credits for the three months ended September 30, 2024, were $0.2 million, down from $0.7 million for the same period in the previous year[9] Liabilities - Total liabilities as of September 30, 2024, were $6.4 million, compared to $8.2 million as of December 31, 2023, indicating a decrease in liabilities[17]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION As filed with the Securities and Exchange Commission on October 8, 2024 Registration Statement No. 333- (Address, including zip code, and telephone number, including area code, of registrant's principal executive offices) Spiro Rombotis President & Chief Executive Officer Cyclacel Pharmaceuticals, Inc. 200 Connell Drive, Suite 1500 Berkeley Heights, NJ 07922 (908) 517-7330 WASHINGTON, DC 20549 FORM S-1 REGISTRATION STATEMENT under the SECURITIES ACT OF 1933 C ...

Revenue and Financial Performance - Revenue for the three and six months ended June 30, 2024, was $4,000 and $33,000, respectively, compared to $373,000 for both periods in 2023, indicating a significant decline in revenue [113][138]. - The company reported a net cash used in operating activities of $3.6 million for the six months ended June 30, 2024, a decrease of $4.6 million from $8.2 million in the same period of 2023 [127]. - As of June 30, 2024, cash and cash equivalents were $6.0 million, down from $10.2 million in 2023, raising concerns about the company's ability to continue as a going concern [125][124]. - The accumulated deficit as of June 30, 2024, was $434.5 million, reflecting the company's ongoing financial challenges [125]. - Total income tax benefit decreased by approximately $0.1 million, from $1.9 million for the six months ended June 30, 2023 to $1.8 million for the six months ended June 30, 2024 [155]. - Total other income decreased by $60,000 from $90,000 for the six months ended June 30, 2023 to $30,000 for the six months ended June 30, 2024 [149]. Research and Development Activities - The Phase 1/2 study of fadraciclib involved 47 heavily pretreated patients, with two partial responses reported in patients with T-cell lymphoma [115][119]. - The Phase 2 proof of concept part of the fadraciclib study is currently enrolling patients with relevant biomarkers, including CDKN2A and/or CDKN2B mutations [120]. - The Phase 1/2 study of plogosertib has treated 15 patients with no dose-limiting toxicities observed, and stable disease has been noted in pretreated patients [122][123]. - Total research and development expenses decreased by $5.6 million from $10.4 million for the six months ended June 30, 2023 to $4.8 million for the six months ended June 30, 2024, representing a 54% decline [144]. - Research and development expenses for the transcriptional regulation program decreased by $3.9 million, primarily due to decreases in manufacturing and non-clinical expenditure [144]. - Overall research and development expenses for the year ended December 31, 2024 are anticipated to decrease compared to 2023, focusing primarily on clinical trial costs [145]. - Research and development expenses represented 60% of operating expenses for the six months ended June 30, 2024, down from 76% in 2023 [143]. - The amount of research and development tax credits is dependent on eligible expenses incurred and may be restricted by future caps introduced by HMRC [156]. Administrative and Future Outlook - General and administrative expenses remained relatively consistent at $3.2 million for the six months ended June 30, 2024 and 2023, representing 40% of operating expenses in 2024 compared to 24% in 2023 [146][147]. - The company expects general and administrative expenditures for the year ended December 31, 2024 to be lower than in 2023 due to cost-cutting efforts [148]. - Future funding requirements will depend on various factors, including the progress of clinical trials and the ability to secure additional financing [132][136]. - The company plans to explore in-licensing and acquisition opportunities to enhance its drug development strategy [131]. - The company expects to fulfill its obligations under a clinical manufacturing agreement by the third quarter of 2024 [139]. Foreign Exchange and Other Financial Metrics - Foreign exchange gains increased by $165,000, from a loss of $161,000 for the six months ended June 30, 2023, to a gain of $4,000 for the six months ended June 30, 2024 [152].

Financial Performance - The company reported revenue of $29,000 for the three months ended March 31, 2024, compared to no revenue for the same period in 2023[108]. - The company had cash and cash equivalents of $2.8 million as of March 31, 2024, down from $11.4 million in the same period of 2023[118]. - The total working capital as of March 31, 2024, was negative $3.5 million, compared to positive $11.6 million in 2023[118]. - The company has an accumulated deficit of $431.2 million as of March 31, 2024[120]. Research and Development Expenses - Research and development expenses totaled $2.8 million for the three months ended March 31, 2024, a decrease of 51% from $5.7 million in the same period of 2023[134]. - Research and development expenses decreased by $2.9 million from $5.7 million in Q1 2023 to $2.8 million in Q1 2024, primarily due to reductions in manufacturing and non-clinical expenditure[137]. - Research and development expenses for the year ended December 31, 2024 are anticipated to decrease compared to 2023 as the company focuses on Phase 1/2 programs[138]. Specific Program Expenses - The transcriptional regulation program (fadraciclib) incurred $1.75 million in expenses, down 57% from $4.09 million in the prior year[134]. - The epigenetic/anti-mitotic program (plogosertib) expenses were $963,000, a decrease of 29% from $1.35 million in the same period of 2023[134]. Operating Activities - The company used net cash of $0.6 million for operating activities in the three months ended March 31, 2024, a significant decrease from $6.9 million in the same period of 2023[121]. General and Administrative Expenses - General and administrative expenses decreased by $0.1 million from $1.645 million in Q1 2023 to $1.582 million in Q1 2024, representing 36% of operating expenses in Q1 2024 compared to 22% in Q1 2023[139]. - General and administrative expenditures for the year ended December 31, 2024 are expected to remain relatively flat compared to 2023[140]. Other Income and Tax Benefits - Total other income decreased by $0.1 million from $0.2 million in Q1 2023 to $0.1 million in Q1 2024, with royalties from an Asset Purchase Agreement contributing $52,000 in Q1 2024[141][142]. - Foreign exchange gains improved from a loss of $87,000 in Q1 2023 to a gain of $1,000 in Q1 2024, reflecting an increase of $88,000[143]. - The total income tax benefit increased by $34,000 from $1.320 million in Q1 2023 to $1.354 million in Q1 2024, remaining flat at approximately $1.3 million for both periods[146]. - Other income (expense), net for the year ended December 31, 2024 will be influenced by foreign exchange rate changes and income from the Asset Purchase Agreement[144]. Future Plans and Expectations - The company plans to enroll patients in the Phase 2 proof-of-concept stage for fadraciclib, focusing on cohorts with relevant biomarkers[113]. - The ongoing Phase 1/2 study of plogosertib has treated 15 patients with no dose-limiting toxicities observed[116]. - The company expects to continue receiving UK research and development tax credits for the year ended December 31, 2024, dependent on eligible expenses incurred[147]. Accounting Policies - There have been no material changes to the company's critical accounting policies during the three months ended March 31, 2024[149].

As filed with the Securities and Exchange Commission on May 6, 2024 Registration Statement No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM S-1 REGISTRATION STATEMENT under the SECURITIES ACT OF 1933 CYCLACEL PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Its Charter) (State or other jurisdiction of incorporation or organization) Delaware 3826 91-1707622 (Primary Standard Industrial Classification Code Number) 200 Connell Drive, Suite 1500 Berkeley Heights ...

As filed with the Securities and Exchange Commission on April 24, 2024 Registration Statement No. 333-278197 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 AMENDMENT NO. 2 TO FORM S-1 REGISTRATION STATEMENT under the SECURITIES ACT OF 1933 CYCLACEL PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Its Charter) (IRS Employer Identification No.) (State or other jurisdiction of incorporation or organization) Delaware 3826 91-1707622 (Primary Standard Industrial Classificati ...

As filed with the Securities and Exchange Commission on April 19, 2024 Registration Statement No. 333-278197 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 AMENDMENT NO. 1 TO FORM S-1 REGISTRATION STATEMENT under the SECURITIES ACT OF 1933 CYCLACEL PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Its Charter) (IRS Employer Identification No.) (State or other jurisdiction of incorporation or organization) Delaware 3826 91-1707622 (Primary Standard Industrial Classificati ...

As filed with the Securities and Exchange Commission on March 22, 2024 Registration Statement No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION FORM S-1 REGISTRATION STATEMENT under the SECURITIES ACT OF 1933 CYCLACEL PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Its Charter) (State or other jurisdiction of incorporation or organization) Delaware 3826 91-1707622 (Primary Standard Industrial Classification Code Number) 200 Connell Drive, Suite 1500 Berkeley Heights, NJ 07922 (908) 5 ...